Unexplained Dyspnea Research Articles

Diagnosing heart failure with preserved ejection fraction in patients with unexplained dyspnoea using left ventricular pressure-volume loops at rest and on exertion

Abstract Background To date, diagnosing heart failure with preserved ejection fraction (HFpEF) remains challenging, especially in euvolaemic patients presenting with unexplained dyspnoea on exertion and reduced exercise capacity. A stepwise approach was introduced with the HFA-PEFF diagnostic algorithm*, in which a relevant number of patients has to undergo invasive workup for a final judgement. Purpose The present study aimed to examine a population of patients with unexplained dyspnoea on exertion, using the diagnostic methods endorsed by the HFA-PEFF algorithm as well as left ventricular (LV) pressure-volume loops at rest, on exertion, and during caval occlusion, in order to identify and describe different phenotypes of HFpEF. Methods We prospectively included patients with unexplained dyspnoea on exertion, a left ventricular ejection fraction (LVEF) of ≥ 50%, and without an obvious cause of the dyspnoea. All patients underwent a comprehensive invasive haemodynamic workup. After invasive rule-out of a haemodynamically relevant coronary artery stenosis, we performed a right heart catheterization at rest (R) and on exertion (E) with an arm ergometer. Real-time continuous pressure-volume loops were obtained using a 7-French conductance catheter at rest, on exertion, and under temporal preload reduction via partial occlusion of the vena cava inferior. Results Thirty patients were included. Two patients had to be excluded from further analysis (one due to a technical failure of the conductance catheter and one with severe hypertension (systolic blood pressure > 200 mmHg) during the assessment). The 28 patients in this analysis had a mean age of 64.4±9.7 years and 57% were female. Eleven patients fulfilled invasively easily obtainable diagnostic criteria of HFpEF (mean pulmonary capillary wedge pressure (mPCWP) at rest ≥ 15 mmHg, exertional mPCWP ≥ 25 mmHg, LV end-diastolic pressure (LVEDP) at rest ≥ 16 mmHg, or exertional LVEDP ≥ 25 mmHg) according to the current guideline*. An additional 15 patients had a normal mPCWP and LVEDP, but fulfilled diagnostic criteria for HFpEF measured by the conductance catheter (time constant of LV relaxation tau > 48 ms and/ or chamber stiffness b > 0.27). We referred to this group as "early HFpEF". Patients with early HFpEF had a significantly higher systolic blood pressure, a worse LV relaxation time, and were more likely to exhibit chronotropic insufficiency compared to the HFpEF group (Table 1). HFpEF patients were characterised by significantly higher natriuretic peptides, LVEDP on exertion, and LV stiffness compared to patients with early HFpEF (pressure-volume loops are depicted in Figure 1). Conclusion Invasive haemodynamic testing for HFpEF in patients with unexplained dyspnoea on exertion via right heart catheterization without obtaining LV pressure-volume loops had a false negative rate of 58%. Better detection, the prognosis, and treatment of this "early HFpEF" population warrants further research.Table 1Figure 1

An elevated mPAP over CO slope by exercise echocardiography predicts outcome in unexplained dyspnea

Abstract Background Exercise pulmonary hypertension, defined by a slope of mean pulmonary artery pressure (mPAP) over cardiac output (CO) >3 mmHg/L/min, measured by invasive exercise hemodynamics, is associated with worse event-free survival in patients with unexplained dyspnea. Whether non-invasive techniques yield similar results has yet to be tested. Purpose To investigate the prognostic value of an mPAP/CO slope > 3 mmHg/L/min determined by exercise echocardiography in suspected heart failure with preserved ejection fraction (HFpEF). Methods This prospective cohort study included patients with unexplained dyspnea defined as dyspnea with an ejection fraction ≥50%. Patients with more than mild valvular heart disease, more than mild pulmonary disease, a history of heart failure, and myocardial or pericardial disease were excluded. A positive HFpEF score was defined as either an HFA-PEFF score of ≥5, including the diastolic stress test and exercise tricuspid regurgitation velocity, or a H2FPEF score of ≥6. The mPAP and CO were obtained by Doppler echocardiography. The primary outcome was the composite endpoint of unplanned cardiovascular hospitalisation (CVH) or all-cause mortality. Results Among the 1922 patients studied (median age 66 [56 to 74] years, 48% women), 39% (n=721) had exercise pulmonary hypertension. After a median follow-up of 14 (10-34) months; 57(3%) patients died and 235 (12%) had at least 1 unplanned CVH. A mPAP/CO slope >3 mmHg/L/min predicted death or unplanned CVH with an odds ratio of 1.51(1.11-2.07) when adjusted for age, sex and pulmonary pressures at rest (Figure 1). The mPAP/CO slope had incremental prognostic value irrespective of whether patients had a positive HFpEF score or not (increase in χ² from 19 to 29; p =0.002) (Figure 2). Conclusion Exercise pulmonary hypertension determined by exercise echocardiography is prognostically relevant as it predicts death and unplanned CVH in patients with unexplained dyspnea. These findings were independent of age, sex, pulmonary hypertension at rest and both the HFpEF scores with the diastolic stress test included.KM exPHTKM exPHT and HFpEF score

Left ventricular volume as a predictor of exercise capacity and functional independence in individuals with preserved ejection fraction

Abstract Background Cardiorespiratory fitness (CRF) is vital for independent living and is a powerful prognostic marker. Increased left ventricular (LV) volume has been linked with high CRF in athletes, but its utility as a diagnostic marker of low CRF across the entire health-disease continuum has yet to be tested. Methods This multi-center international cohort from Australia and Belgium examined the relationship between ventricular size on resting echocardiography and CRF (peakVO2 from cardiopulmonary exercise testing [CPET] or CPET with simultaneous echocardiography) in individuals with preserved LV ejection fraction (≥50%). LV end-diastolic volume (LVEDV) and LVEDV indexed to body surface area (LVEDVi) were tested as predictors of very low CRF (CRF associated with functional disability - peakVO2 < 1100ml or <18 ml/kg/min) and compared against other candidate measures of systolic and diastolic cardiac function that have been associated with heart disease. Thresholds for absolute and indexed LVEDV which best distinguished between lower and higher CRF status were identified. Results 2876 individuals (251 healthy non-athletes, 309 elite endurance athletes, 1969 individuals with unexplained dyspnea, 347 individuals with heart failure with preserved ejection fraction) were included. For the entire cohort, LVEDV had the strongest univariate association with peakVO2 (R2 = 0.45, standardized [std] β 0.67, p< 0.001) and, remained the strongest independent predictor of peakVO2 after adjusting for age, sex and body mass index (std β 0.44, p < 0.001). The relationship between LVEDV and VO2peak differed based on health/disease status (Figure 1). LVEDV demonstrated the greatest diagnostic capability in identifying functional disability (LVEDV AUC 0.72; LVEDVi AUC 0.71, Figure 2), outperforming ejection fraction, diastolic velocities, atrial volumes and pulmonary artery pressure estimates. The probability of achieving a peak VO2 below the threshold required for functional independence was highest for smaller ventricular volumes with LVEDV and LVEDVi of 88ml and 57 ml/m2 proving the optimal cut-points, respectively. Conclusions A small LVEDV is associated with a higher probability of poor exercise capacity, failure to achieve the peak VO2 required for functional independence and is the strongest independent echocardiographic predictor of CRF across the health-disease continuum.Figure 1.Ventricular Size and CRFFigure 2.Predictors of CRF status

The prognostic value of contrast stress echocardiography in a real-world population of symptomatic patients without known coronary artery disease

Abstract Background Coronary artery disease (CAD) is the leading cause of mortality and morbidity worldwide. In addition to diagnosis, non-invasive tests may also provide prognostic information useful in the risk stratification and management of CAD patients. Stress echocardiography (SE) is an accurate, non-invasive method for the detection of obstructive CAD. However, in real-world clinical practice the test performance may vary among different centres, depending on availability, local protocols, and operator expertise. Purpose To evaluate the prognostic value of contrast SE in a real-world population of symptomatic patients without known CAD. Methods This was a cohort follow-up study of patients without known CAD and symptoms of atypical chest pain, unexplained dyspnoea or palpitations who were referred to the echocardiography lab of a tertiary hospital for SE between January 2020 and December 2021. Patients with resting regional wall motion abnormalities were excluded. All patients underwent treadmill exercise stress echocardiography (ESE) or dobutamine stress echocardiography (DSE) if unable to exercise. Contrast agents were used in almost all patients (99%). The study population was followed-up for at least 2 years after SE by phone and/or electronic hospital records. Cardiac outcome was defined as anatomically or functionally significant stenosis on angiography, revascularization, acute coronary syndrome (ACS), or cardiac-related death. Results The study comprised 266 patients (mean age 58±12 years, 63% male) who underwent either ESE (58%) or DSE (42%). The patients' details are reported in Table 1. The most common indication for the exam was atypical chest pain, with a prevalence of 73%. SE exams were positive for inducible ischaemia in 14 (5%) patients. Symptoms during the exam were present in 3 (21%) patients with positive SE and 4 patients (2%) with negative SE (p=0.004). No serious complications (sustained ventricular tachycardia, myocardial infarction, or death) were recorded. During the follow-up (median 30, IQR 23–38 months), 264 patients (99%) were successfully contacted. Cardiac outcome occurred in 10 patients. Among 14 patients with positive SE, 8 underwent revascularization due to significant coronary artery stenosis. Among 250 patients with negative SE, 1 underwent revascularization due to significant coronary artery stenosis and 1 presented with ACS 13 months after the test (both patients underwent DSE). Negative predictive value was 99% over a median follow-up of 30 months, corresponding to an annualized event rate of 0.32% per year. A positive SE was significantly associated with cardiac outcome (log-rank test p<0.0001, Figure 1). Conclusion Contrast SE carries significant prognostic implications in symptomatic patients without known CAD. A positive test is strongly associated with the need for revascularization, while a normal test result has an excellent negative predictive value regarding cardiovascular morbidity and mortality.Figure 1

The added value of cardiopulmonary exercise testing in the diagnosis of heart failure with preserved ejection fraction

Abstract Background Diagnosing heart failure with preserved ejection fraction (HFpEF) is challenging. Two validated algorithms, the HFA-PEFF and H2FPEF scores, have been proposed to guide our clinical practice. Many patients are categorized into an intermediate probability for HFpEF, representing a diagnostic "gray zone." This necessitates further evaluation, including right heart catheterization (RHC) at rest and possibly during exercise, to confirm or exclude the diagnosis. RHC, while informative, is resource-consuming and requires execution in specialized centers. Cardiopulmonary exercise testing (CPET) may offer a non-invasive and cost-effective alternative for differential dyspnea diagnosis. Purpose To evaluate the role of CPET in the diagnostic algorithm of unexplained dyspnea/suspected HFpEF. Methods This single-center retrospective study analyzed patients with a left ventricular ejection fraction (LVEF) ≥ 50% who underwent CPET for unexplained dyspnea from 2016 to 2020. We assessed HFpEF probability using the H2FPEF score and the HFA-PEFF algorithm. We hypothesized that specific CPET parameters (VO2 peak< 80% of predicted and/or VE/VCO2 slope > 35) might provide complementary information to the HFpEF probability scores. Additionally, we hypothesized that CPET could help identifying HFpEF in patients with intermediate probability in a subcohort of patients who underwent exercise RHC. Results Out of 103 patients, 61 (59%) were categorized as intermediate probability of HFpEF according to the HFA-PEFF score, and 59 (57%) according to the H2FPEF score. CPET results (VO2 peak and VE/VCO2 slope) were not associated with the pre-test probability of HFpEF as defined by either of the two scores. Exercise RHC was performed in 26 (43%) and in 27 (46%) patients with intermediate HFA-PEFF score and intermediate H2FPEF score, respectively. Among these patients with intermediate HFpEF probability, VO2 peak < 80% and/or VE/VCO2 slope > 35 had a good specificity and positive predictive value for HFpEF, as compared with exercise RHC (Table). Conclusions CPET provides complementary information to HFA-PEFF and H2FPEF scores. In particular, our results suggest that CPET may reclassify as HFpEF over 25% of patients with an intermediate HFpEF probability according to either the HFA-PEFF score or the H2FPEF score, potentially obviating the need for RHC. Thus, CPET might be incorporated into the HFpEF diagnostic algorithms.Table

Patent Foramen Ovale and Oxygenation in Patients with Cystic Fibrosis.

Patent foramen ovale (PFO) affects about 25% of the population. We studied outcomes in cystic fibrosis (CF). We conducted a case-control study of patients with CF (PwCF) and age and sex-matched controls who underwent agitated saline contrast (bubble) echocardiography, 1998-2020. We assessed PFO impacts using linear, logistic, quasipoisson and proportional hazards models. 59 of 64 PwCF and 88 of 93 controls underwent bubble studies to investigate unexplained hypoxemia or dyspnea. PwCF had higher mean pulmonary artery pressure (PAP, 6.9 mm Hg, 95% Confidence Interval [CI] = 2.35-11.4), reduced tricuspid annular plane systolic excursion (TAPSE, -3.78 mm, CI = -5.64 to -1.93) and similar right ventricular diastolic sizes. Absent hypoxemia, PFO incidence was similar between PwCF and controls; with hypoxemia, PFO was more common in CF (Odds Ratio [OR] = 5.00, CI = 1.32-19.0). In CF, oxygen supplementation occurred at a percent predicted forced expiratory volume in 1 s (FEV1%) 22.5 points higher with PFO. Adjusted for FEV1%, PFO was associated with 0.59 more prior year pulmonary exacerbations (CI = 0.20-0.98) and shorter time to next exacerbation (Hazard Ratio = 1.86, CI = 1.06-3.26). Associations between PFO and hypoxemia or exacerbations were insensitive to PAP, TAPSE and CF transmembrane regulator protein modulator treatments. PFO was not associated with CF time to death or lung transplantation (median 1.87 years) adjusted for age, sex, FEV1% and prior year exacerbation counts. PFO in CF is associated with hypoxemia at higher FEV1% and more pulmonary exacerbations but not survival.

S3889 Unexplained Dyspnea: A Rare Case of Crohn’s Disease Complicated with Bronchiolitis Obliterans

S3889 Unexplained Dyspnea: A Rare Case of Crohn’s Disease Complicated with Bronchiolitis Obliterans

Frequency of Asymptomatic Deep Vein Thrombosis in Hospitalized Patients With Acute Exacerbation of Chronic Obstructive Pulmonary Disease (COPD).

Acute exacerbations of chronic obstructive pulmonary disease (COPD) are always associated with high mortality. Because of the presence of some concomitant risk factors such as immobilization and bronchial superinfection, patients who are admitted for acute exacerbations of COPD are generally considered to be at moderate risk for the development of venous thromboembolism. Thromboembolism is a cause of unexplained dyspnea, exacerbations, and mortality in COPD. This study aims to determine the frequency of asymptomatic deep vein thrombosis (DVT) in patients with acute exacerbations of COPD presented at a tertiary care hospital. This is a descriptive cross-sectional study conducted at the Department of Chest Medicine, Jinnah Postgraduate Medical Center (JPMC), Karachi. A duplex ultrasound study of both lower limbs was performed by a sonologist to assess asymptomatic DVT in patients with acute exacerbations of COPD. The mean age of the sample was 59.64 ± 9.711 years. Out of 106 patients, 95 (90%) were male and 11 (10%) were female. Asymptomatic DVT was found in 16 (15%) patients with acute exacerbations of COPD. Male patients exhibited a higher incidence of DVT, with 12 cases versus four in females, a statistically significant finding (p=0.03). Additionally, DVT was significantly more prevalent among patients with restricted mobility, with all 16 cases occurring in this group (p=0.006). Age did not show a statistically significant difference in DVT occurrence between patients above and below 59 years. Deep venous thrombosis is a common occurrence in COPD exacerbations. It is a risk factor for pulmonary embolism that carries a high mortality. All patients with COPD exacerbations may need to be assessed for thromboembolic events. COPD morbidity and mortality are continually rising despite efforts to recognize new phenotypes and treatments. The cause may be the association of unrecognized and untreated thromboembolism. Prompt diagnosis and treatment with anticoagulants in COPD patients may lead to a better prognosis.

Post-Pulmonary Embolism Phenotypes Described by Invasive Cardiopulmonary Exercise Testing

BackgroundPost pulmonary embolism (PE) dyspnea is common. Existing non-invasive studies have demonstrated that post PE dyspnea is associated with elevations in right ventricular afterload, dead space ventilation, and deconditioning. We aimed to use invasive cardiopulmonary exercise testing (iCPET) parameters in patients with post PE dyspnea to identify unique physiologic phenotypes. Research QuestionAre there distinct post pulmonary embolism dyspnea physiologic phenotypes described with iCPET? Study Design and MethodsPatients were enrolled at the time of acute PE and through our pulmonary hypertension and dyspnea clinic. ICPET was performed if there was high suspicion for pulmonary hypertension or if there was unexplained dyspnea. A hierarchical cluster analysis was performed to identify dyspnea phenotypes. ICPET parameters assessing pulmonary hemodynamics, ventilation, and peripheral oxygen utilization were then compared within and across each cluster and with iCPET controls against peak oxygen consumption (Peak VO2). Results173 patients were enrolled. Sixty-seven patients underwent iCPET. All patients had reductions in Peak VO2 and peak cardiac index relative to controls. Three clusters were identified. Cluster one was defined by having elevated RV afterload and impaired ventilatory efficiency. Cluster two had elevated RV afterload with reductions in respiratory mechanics. Cluster three had mild derangement in RV afterload with mild reductions in peak cardiac output. InterpretationiCPET reveals significant heterogeneity in post PE dyspnea. Three phenotypes are characterized by differences in RV afterload, ventilatory efficiency, respiratory mechanics, and peripheral oxygen utilization.

An evidence-based screening tool for heart failure with preserved ejection fraction: the HFpEF-ABA score.

Heart failure with preserved ejection fraction (HFpEF) is under-recognized in clinical practice. Although a previously developed risk score, termed H2FPEF, can be used to estimate HFpEF probability, this score requires imaging data, which is often unavailable. Here we sought to develop an HFpEF screening model that is based exclusively on clinical variables and that can guide the need for echocardiography and further testing. In a derivation cohort (n = 414, 249 women), a clinical model using age, body mass index and history of atrial fibrillation (termed the HFpEF-ABA score) showed good discrimination (area under the curve (AUC) = 0.839 (95% confidence interval (CI) = 0.800-0.877), P < 0.0001). The performance of the model was validated in an international, multicenter cohort (n = 736, 443 women; AUC = 0.813 (95% CI = 0.779-0.847), P < 0.0001) and further validated in two additional cohorts: a cohort including patients with unexplained dyspnea (n = 228, 136 women; AUC = 0.840 (95% CI = 0.782-0.900), P < 0.0001) and a cohort for which HF hospitalization was used instead of hemodynamics to establish an HFpEF diagnosis (n = 456, 272 women; AUC = 0.929 (95% CI = 0.909-0.948), P < 0.0001). Model-based probabilities were also associated with increased risk of HF hospitalization or death among patients from the Mayo Clinic (n = 790) and a US national cohort across the Veteran Affairs health system (n = 3076, 110 women). Using the HFpEF-ABA score, rapid and efficient screening for risk of undiagnosed HFpEF can be performed in patients with dyspnea using only age, body mass index and history of atrial fibrillation.

A 58-year-old man with unexplained cough and dyspnoea.

A 58-year-old man with unexplained cough and dyspnoea.

The roles of exercise stress echocardiography for the evaluation of heart failure with preserved ejection fraction in the heart failure pandemic era.

Heart failure with preserved ejection fraction (HFpEF) accounts for nearly 70% of all HF and has become the dominant form of HF. The increased prevalence of HFpEF has contributed to a rise in the number of HF patients, known as the "heart failure pandemic". In addition to the fact that HF is a progressive disease and a delayed diagnosis may worsen clinical outcomes, the emergence of disease-modifying treatments such as sodium-glucose transporter 2 inhibitors and glucagon-like peptide-1 receptor agonists has made appropriate and timely identification of HFpEF even more important. However, diagnosis of HFpEF remains challenging in patients with a lower degree of congestion. In addition to normal EF, this is related to the fact that left ventricular (LV) filling pressures are often normal at rest but become abnormal during exercise. Exercise stress echocardiography can identify such exercise-induced elevations in LV filling pressures and facilitate the diagnosis of HFpEF. Exercise stress echocardiography may also be useful for risk stratification and assessment of exercise tolerance as well as cardiovascular responses to exercise. Recent attention has focused on dedicated dyspnea clinics to identify early HFpEF among patients with unexplained dyspnea and to investigate the causes of dyspnea. This review discusses the role of exercise stress echocardiography in the diagnosis and evaluation of HFpEF.

Quantification of breathing irregularity for the diagnosis of dysfunctional breathing using proportional tidal volume variation: a cross-sectional, retrospective real-world study

ObjectivesTo develop a statistical approach that provides a quantitative index measuring the magnitude of the irregularity of the breathing response to exercise for the diagnosis of dysfunctional breathing.DesignCross-sectional, retrospective, real-world...

Treatment of recurrent pulmonary thromboembolism with ecosonic endovascular system

Venous thromboembolism is a collective term that describes two diseases, pulmonary thromboembolism (PTE) and deep vein thrombosis, with or without symptoms but often accompanying each other. Pulmonary thromboembolism (PTE) develops in most cases due to thrombus formation in the deep veins of the lower extremities and migrates to the pulmonary artery and/or its branches. It is a preventable disease with high mortality and morbidity and includes diagnostic difficulties. Recurrence may occur despite treatment in 5-23% of PTE cases. Patients may apply to the hospital with symptoms such as unexplained dyspnea, stabbing or atypical chest pain, hemoptysis, and syncope. We aimed to present the patient who had chronic deep vein thrombosis (DVT) and was frequently hospitalized due to recurrent massive PTE. In our case, disease status requires catheter thrombolytic therapies two times in three months.

Machine learning for development of ECG-based prediction models for atrial fibrillation, thromboembolism and mortality in patients with heart failure

Abstract Background Heart failure (HF) is a worldwide epidemic affecting more than 64 million people. Given its massive burden both socially and economically, early identification of individuals at risk for complications is important. Purpose To test the predictive performance of non-invasive models from 12-lead digitalized electrocardiography (ECG) and cycle ergometer for adverse outcome in individuals with heart failure. Methods 598 Patients scheduled for right heart catheterization due to unexplained dyspnea were screened. All ECG recorded at admission were further analysed using the software "ECG-Precision-Analysis V-1-2023" to measure the duration of amplified p-wave (APWD at 175mm/sec, 80mm/mV) and to confirm the diagnosis of inter-atrial block. Ergometer was performed in a supine position with increasing intensity adapted to individual capacity (25 or 50W). The maximum physical capacity (Watt-max) was determined. Follow-up (FU) was scheduled at 12-,36-, 60- and 120-month after discharge with the primary endpoint as MACCE (a composite of new onset of AF, ischemic stroke and peripheral embolism) in at baseline event-free patients and the secondary endpoint as all-cause mortality in the total cohort. Three machine learning (ML) algorithms (COX regression, BSR and LASSO regression) were used to select candidate variables and establish predictive models for MACCE and all-cause mortality. Model evaluation was performed in terms of discriminatory power using C-statistics for each endpoint. Results Prediction models developed using machine learning (ML) algorithms (COX regression, BSR and LASSO regression) identified Watt-max and/or APWD as core components for MACCE and mortality prediction . APWD and Watt-max were key components of ML models for prediction of thromboembolic risk and AF (MACCE) and reached accurate diagnostic performances (C-statistics up to 0.74), moreover, another model consisted of APWD and aIAB (advanced inter-atrial block) was established to serve as a reference to ML models with moderate performance for MACCE (mean C-statistics &amp;lt;0.70). All ML models for prediction of all-cause mortality included Watt-max and achieved C-statistics &amp;gt; 0.75. Conclusions In patients with heart failure, the combination of APWD, aIAB and maximum excercice capacity allow to identify patients at risk for AF and stroke, whereas mortality is predominantly predicted by maximum exercise capacity but not APWD.Kaplan-Meier curves for MACCE/MortalitytimeROC curves for MACCE/Mortality

The Shrinking Lung Syndrome or Retracted Lung Syndrome During Systemic Lupus Erythematosus: About Two Cases

The shrinking lung syndrome represents an uncommon complication associated with systemic autoimmune diseases, primarily systemic lupus ery the matosus, but also Sjögren's syndrome and polymyositis. It is a condition that should be considered in any patient with an autoimmune disease presenting unexplained dyspnea. This syndrome is characterized by reduced lung volumes, elevation of the diaphragm, and restrictive physiology without significant parenchymal involvement. The article emphasizes the crucial role of thoracic CT in the diagnosis of the shrinking lung syndrome. Thoracic CT plays an essential role in identifying characteristic radiological signs such as pulmonary atelectasis and elevation of the diaphragmatic domes. These specific radiological features significantly contribute to confirming the diagnosis by excluding other potential causes of dyspnea, notably pulmonary embolism.

Characteristics and outcomes of gemcitabine-associated pulmonary hypertension.

Despite its known cardiac and lung toxicities, the chemotherapy drug gemcitabine has only rarely been associated with pulmonary hypertension (PH), and the underlying mechanism remains unclear. The objective of the present study was to assess the association between gemcitabine and PH. We identified incident cases of precapillary PH confirmed by right heart catheterisation in patients treated with gemcitabine from the French PH Registry between January 2007 and December 2022. The aetiology, clinical, functional, radiological and haemodynamic characteristics of PH were reviewed at baseline and during follow-up. A pharmacovigilance disproportionality analysis was conducted using the World Health Organization (WHO) pharmacovigilance database. We identified nine cases of pulmonary arterial hypertension, either induced (in eight patients) or exacerbated (in one patient) by gemcitabine. Patients exhibited severe precapillary PH, with a median mean pulmonary arterial pressure of 40 (range 26-47) mmHg, a cardiac index of 2.4 (1.6-3.9) L·min-1·m-2 and a pulmonary vascular resistance of 6.3 (3.1-12.6) Wood units. The median time from the initiation of gemcitabine to the onset of PH was 7 (4-50) months, with patients receiving a median of 16 (6-24) gemcitabine injections. Six patients showed clinical improvement upon discontinuation of gemcitabine. In the WHO pharmacovigilance database, we identified a significant signal with 109 cases reporting at least one adverse event related to PH with gemcitabine. Both clinical cases and pharmacovigilance data substantiate a significant association between gemcitabine use and the onset or worsening of precapillary PH. The observed improvement following the discontinuation of treatment underscores the importance of PH screening in gemcitabine-exposed patients experiencing unexplained dyspnoea.

Bronchoalveolar Lavage Fluid Cytology of Deployed Military Personnel With Chronic Respiratory Symptoms From the STAMPEDE III Study.

Deployed military personnel may be at risk for developing acute and chronic lung disease. Prior studies of this patient population have revealed that unexplained exertional dyspnea is the most common diagnosis despite an extensive evaluation. There is a concern that an occult disorder may be affecting this population. This study evaluated the role for bronchoalveolar lavage (BAL) fluid analysis in the evaluation of chronic deployment-associated dyspnea. Military personnel who reported chronic respiratory symptoms were evaluated as part of the Study of Active Duty Military for Pulmonary Disease Related to Environmental Deployment Exposures III study. Participants underwent bronchoscopy with BAL as part of a standardized evaluation. A total of 308 patients with a mean age of 38 ± 8.6 years underwent bronchoscopy with BAL. BAL cell-count percentages of macrophages, lymphocytes, neutrophils, and eosinophils were: 76.2 ± 17.0%, 16.3 ± 13.4%, 6.6 ± 8.9%, and 0.9 ± 3.2%, respectively. There was no clear differentiation between groups based on increases in lymphocyte counts (P = .640), although lymphocyte values were more elevated (21.4 ± 12.1%) in the interstitial lung disease category. Neutrophil counts (6.6 ± 8.9%) were elevated compared to the reported normal reference values and were increased in the isolated pulmonary function test abnormality (9.4 ± 11.6%), large airway disorder (10.0 ± 7.5%), miscellaneous (10.9 ± 20.2%), and obstructive lung disease (11.0 ± 15.6%) groups. Eosinophil counts were within normal limits (0.9 ± 3.2%) and showed no differences between groups (P = .545); asthma patients trended higher (1.6 ± 5.7%). BAL counts for the exertional dyspnea group were within normal reference values and showed no differences from the entire cohort. The addition of BAL cytology did not help differentiate those patients with unexplained dyspnea from other etiologies.

A non-invasive nomogram for predicting heart failure with preserved ejection fraction in taiwanese outpatients with unexplained dyspnea and fatigue

BackgroundWhile Reddy proposed the H2FPEF diagnostic algorithm to aid in diagnosing heart failure with preserved ejection fraction (HFpEF), certain parameters like age and obesity are not suitable for Asian population, especially given the increasing incidence of HFpEF in younger individuals. Therefore, this study aimed to develop an easy-to-use nomogram with non-invasive indices that can be used in outpatient clinics in Taiwan to quickly estimate the probability of HFpEF and help decide whether further invasive cardiopulmonary exercise test (CPET) is needed. MethodsOutpatients with unexplained dyspnea and fatigue were recruited divided into HFpEF (n = 64) and non-HFpEF (n = 34) groups based on invasive CPET and echocardiography. Multivariate logistic regression analyses identified independent noninvasive variables for developing an HFpEF nomogram. The nomogram's performance was assessed and validated using the concordance index (C-index), area under the curve (AUC), calibration curves, and decision curve analysis. ResultsMultivariate logistic regression analyses identified five independent noninvasive variables for developing an HFpEF nomogram, including dyslipidemia (OR = 5.264, p = 0.010), diabetes (OR = 3.929, p = 0.050), left atrial area (OR = 1.130, p = 0.046), hemoglobin <13 g/dL (OR = 5.372, p = 0.010), and NT-proBNP ≥245 pg/mL (OR = 5.108, p = 0.027). The nomogram showed good discriminatory ability (C-index = 0.842) and calibration performance (p = 0.873) and high net benefit (0.1−0.95). Notably, the HFpEF nomogram showed better diagnostic accuracy than the H2FPEF score model in predicting Taiwanese HFpEF patients (AUC: 0.873 vs. 0.608, p = 0.0006). ConclusionThe noninvasive HFpEF nomogram provides a preliminary estimation of the probability of HFpEF in Taiwanese outpatients with unexplained dyspnea and fatigue, which may help the decision-making on further invasive CPET.

Repetitive sulfur dioxide exposure in mice models post-deployment respiratory syndrome.

Soldiers deployed to Iraq and Afghanistan have a higher prevalence of respiratory symptoms than nondeployed military personnel and some have been shown to have a constellation of findings on lung biopsy termed post-deployment respiratory syndrome (PDRS). Since many of the subjects in this cohort reported exposure to sulfur dioxide (SO2), we developed a model of repetitive exposure to SO2 in mice that phenocopies many aspects of PDRS, including adaptive immune activation, airway wall remodeling, and pulmonary vascular (PV) disease. Although abnormalities in small airways were not sufficient to alter lung mechanics, PV remodeling resulted in the development of pulmonary hypertension and reduced exercise tolerance in SO2-exposed mice. SO2 exposure led to increased formation of isolevuglandins (isoLGs) adducts and superoxide dismutase 2 (SOD2) acetylation in endothelial cells, which were attenuated by treatment with the isoLG scavenger 2-hydroxybenzylamine acetate (2-HOBA). In addition, 2-HOBA treatment or Siruin-3 overexpression in a transgenic mouse model prevented vascular remodeling following SO2 exposure. In summary, our results indicate that repetitive SO2 exposure recapitulates many aspects of PDRS and that oxidative stress appears to mediate PV remodeling in this model. Together, these findings provide new insights regarding the critical mechanisms underlying PDRS.NEW & NOTEWORTHY We developed a mice model of "post-deployment respiratory syndrome" (PDRS), a condition in Veterans with unexplained exertional dyspnea. Our model successfully recapitulates many of the pathological and physiological features of the syndrome, revealing involvement of the ROS-isoLGs-Sirt3-SOD2 pathway in pulmonary vasculature pathology. Our study provides additional knowledge about effects and long-term consequences of sulfur dioxide exposure on the respiratory system, serving as a valuable tool for future PDRS research.